Treatment of Patients Diagnosed with Giant Cell Tumor of Bone: Experience of a Philanthropic Hospital in the State of Piauí, Brazil / Tratamento de pacientes com diagnóstico de tumor ósseo de células gigantes: Experiência de um hospital filantrópico no Piauí, Brasil

Abstract Objective To evaluate the treatment of patients with giant cell tumors of bone treated from 2009 to 2019 in a philanthropic hospital, as well as to try and determine the regional clinical and epidemiological profile, aiming to enrich the Brazilian data set and compare our findings with those of the literature. Methods An analytical, observational, and cross-sectional study with retrospective data collection and a quantitative approach, analyzing medical records of patients with giant cell tumors treated at a philanthropic hospital from 2009 to 2019. Results We evaluated 49 medical records; 55.1% of the patients were women, 53.1% were aged between 20 and 40 years, 69.4% of the cases were Campanacci grade III, and 30.6% affected the proximal end of the tibia. The rate of pathological fractures secondary to the tumor and pulmonary metastasis was low. More than 69% of the patients underwent intralesional surgery. Recurrence occurred in 16.3% of the cases. Conclusion The criteria used for the diagnosis, classification, and treatment at our service followed the standards established by the literature, and they can guide further research and improve local prognosis in the future.

Resumo Objetivo Avaliar o tratamento fornecido a pacientes com diagnóstico de tumor de células gigantes ósseo atendidos no período de 2009 a 2019 em um hospital filantrópico, bem como determinar o perfil clínico e epidemiológico regional, visando enriquecer os dados nacionais e comparar os achados com a literatura existente. Métodos Estudo analítico, observacional e transversal, com coleta retrospectiva e abordagem quantitativa, com análise de prontuários de pacientes diagnosticados com tumor de células gigantes atendidos em um hospital filantrópico no período de 2009 a 2019. Resultados Foram avaliados 49 prontuários, sendo que 55,1% eram de mulheres, com 53,1% dos casos na faixa etária de 20 a 40 anos, 69,4% de casos de grau III de Campanacci, e 30,6% acometendo a extremidade proximal da tíbia. Observou-se baixo índice de fratura patológica secundária ao tumor e de metástase pulmonar. A cirurgia intralesional foi realizada em 69,5% dos pacientes. Houve recidiva em 16,3% dos casos. Conclusão Os critérios usados para diagnóstico, classificação e tratamento em nosso serviço seguiram os padrões estabelecidos pela literatura, e podem orientar novas pesquisas e melhorar o prognóstico local futuramente.

A single-center experience with giant cell tumors of sphenoid bone and clivus.

OBJECTIVE: To present pathologic, clinical, and treatment findings for giant cell tumors (GCTs) of sphenoid bone and clivus. METHODS: We describe the optimal treatment algorithm in patients with a histopathologic diagnosis of bone GCT by presenting the effects of denosumab treatment in both pediatric and adult patients with GCT undergoing endoscopic transnasal surgery. Clinicopathologic correlation is crucial for the differential diagnosis of GCT and the choice of treatment modality. CONCLUSION: GCT of bone is a local aggressive tumor that accounts for about 3%-7% of all bone tumors. GCTs located in the cranium are extremely uncommon neoplasms. There are no defined guidelines for the treatment of GCTs in skull base. Following surgical resection of the tumor, the addition of denosumab treatments to radiotherapy has a significant role in preventing the recurrence of GCT and in promoting regression of residual tumor size.

The Efficacy of Radiofrequency Ablation for Bone Tumors Unsuitable for Radical Excision.

BACKGROUND: Bone tumors can cause severe pain and poor quality of life due to recurrence and non-achievement of complete remission after surgery, chemotherapy, or radiotherapy. Radiofrequency ablation (RFA) can be considered for minimally invasive treatment of bone tumors that are difficult to radically excise. In this study, RFA was performed for bone tumors that were difficult to radically excise and did not respond to surgery, chemotherapy, or radiotherapy due to their large sizes and/or locations. The purpose of this study was to retrospectively analyze the clinical characteristics and survival rates of bone tumors after RFA and provide one more treatment option for the future. METHODS: There were 43 patients with bone tumors who underwent percutaneous RFA at our hospital from April 2007 to October 2017. The median age of the patients was 59 years (range, 31-75 years), and the median follow-up duration was 67.2 months (range, 10.2-130.5 months). Of the 43 patients, 26 were male and 17 were female. Thirty-four cases were metastatic bone tumors, 5 were chordomas, 3 were osteosarcomas, and 1 was a giant cell tumor. Pain and functional ability of the patients were evaluated using a visual analog scale (VAS) and the Musculoskeletal Tumor Society (MSTS) functional scoring system, respectively. Scores were recorded preoperatively, 1 week postoperatively, and 4 weeks postoperatively. The 1-year, 2-year, and 5-year survival rates were evaluated using the Kaplan-Meier method. RESULTS: The mean VAS score was 8.21 preoperatively. The mean VAS score at 1 week, 4 weeks, 12 weeks, and 24 weeks postoperatively were 3.91, 3.67, 3.31, and 3.12, respectively. The mean preoperative MSTS score was 64.0% (range, 32%-87%). The mean postoperative MSTS score was 71.0% (range, 40%-90%). The 1-year, 2-year, and 5-year survival rates were 95.3%, 69.8%, and 30.2%, respectively. CONCLUSIONS: As per our study findings, RFA was effective in reducing pain and improving functional ability of patients with bone tumors that were difficult to radically excise.

Minimally Invasive Spinal Stabilization with Denosumab before Total Spondylectomy for a Collapsing Lower Lumbar Spinal Giant Cell Tumor.

A 21-year-old man consulted our hospital for treatment of a spinal giant cell tumor (GCT) of Enneking stage III. Lower lumbar-spine tumors and severe spinal canal stenosis are associated with high risk for surgical mor-bidity. Stability was temporarily secured with a percutaneous pedicle screw fixation in combination with deno-sumab, which shrank the tumor. Total en bloc spondylectomy was then performed 6 months after initiation of denosumab, and the patient was followed for 3 years. There was no local recurrence, and bony fusion was obtained. Minimally invasive surgery and denosumab allowed safer and easier treatment of a collapsing lower lumbar extra-compartmental GCT.

Denosumab for Effective Tumor Size Reduction in Patients With Giant Cell Tumors of the Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: Denosumab is a human monoclonal antibody that has been used successfully in the treatment of giant cell tumors of bone. These tumors are rare and, in principle, benign, but they are highly aggressive, locally advanced, osteolytic bone tumors that can metastasize to the lungs. Denosumab is an effective treatment when these tumors cannot be surgically removed or when surgical resection is likely to lead to severe morbidity (eg, loss of limbs or joints). The aim of this systematic review and meta-analysis was to investigate patients with giant cell tumors of bone who experienced tumor progression during treatment with denosumab and to compare them with patients who experienced reduction of their giant cell tumors of bone during treatment with denosumab. METHODS: Embase, Cochrane Library, and MEDLINE/PubMed databases were searched for trials submitted by January 7, 2020, that reported the efficacy and safety of denosumab in patients with giant cell tumors of bone. RESULTS: Sixty studies were reviewed, involving a total of 1074 patients who had giant cell tumors of bone and were treated with denosumab. Of the 60 studies, 58% of the patients were from case series studies, 39% from open-label phase II studies, and 3% from case reports. The response rate for denosumab as a treatment for giant cell tumors of bone was 97.5%, with statistical significance (P < .0001). Pain in the limbs was statistically the most common adverse event for denosumab treatment in case series studies (P < .0001). No treatment-related deaths occurred in the reviewed studies. CONCLUSION: Cumulative evidence supports the addition of surgery to optimal medical therapy with denosumab to reduce tumor size, clinical symptoms, and mortality among patients with giant cell tumors of bone.

Making sense of giant cell lesions of the jaws (GCLJ): lessons learned from next-generation sequencing.

Next-generation sequencing has revealed mutations in several bone-related lesions and was recently used to uncover the genetic basis of giant cell lesions of the jaws (GCLJ). Consistent with their benign nature, GCLJ show a low tumor mutation burden. They also harbor somatic, heterozygous, mutually exclusive mutations in TRPV4, KRAS, or FGFR1. These signature mutations occur only in a subset of lesional cells, suggesting the existence of a 'landscaping effect', with mutant cells inducing abnormal accumulation of non-mutant cells that form the tumor mass. Osteoclast-rich lesions with histological similarities to GCLJ can occur in the jaws sporadically or in association with genetically inherited syndromes. Based on recent results, the pathogenesis of a subgroup of sporadic GCLJ seems closely related to non-ossifying fibroma of long bones, with both lesions sharing MAPK pathway-activating mutations. In this review, we extrapolate from these recent findings to contextualize GCLJ genetics and we highlight the therapeutic implications of this new information. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A case of giant cell tumor of the tendon sheath in an elderly patient: diagnostic difficulties and therapeutic options.

Giant cell tumor of the tendon sheath (GCTTS) is a benign tumor with a high recurrence rate of up to 50%. The lesion may appear anywhere in the synovium; the nature of this tumor is still controversial, however recent data shows that tenosynovial giant cell tumors (TGCTs) could be clonal neoplastic tumors. Most lesions of GCTTS produce one or more discrete nodules, while the radiological features can include soft-tissue masses with or without bone destruction. In an effort to advance in the understanding of GCTTS pathogenesis, we decided broadly investigate the immunophenotypic profile, of a TGCT in a 69-year-old female patient.

Life is precious: Sarcoma/giant-cell tumors survivors' perspectives on their psychological journey.

OBJECTIVES: Although surviving bone resection/limb salvage surgery treatment is the beginning of the journey towards recovery, the importance of providing patients with post-operative psychological support is often overlooked by health professionals. Hence, patients typically are left to their own devices in terms of ensuring their mental health and well-being. Methodological Approach and Participants: This qualitative analysis of seven long-term sarcoma survivors' reflective journal entries provides insights into the different phases of distress, resilience building, resilient growth and advice-giving that they moved through during their survivorship journey. INTERPRETATION: Our findings identify the fragility of patient resilience and highlight areas for future research.

Cryotherapy efficacy and safety as local therapy in surgical treatment of musculoskeletal tumours. A retrospective case series of 143 patients.

Cryotherapy, also called Cryoablation (CA), is a technique that provides a local treatment to various pathological conditions. In Musculoskeletal tumours management, Cryoablation is well accepted and validated as a treatment in palliative cures for metastatic patients. Recently, CA has been proposed also as an alternative to radiofrequency ablation in osteoid osteoma and other benign tumour treatment with promising results. Cryotherapy with argon ice-balls as local adjuvant in open surgery is a tool that can provide enlargement of surgical margins if used properly. There is still not enough evidence supporting use of cryotherapy as local adjuvant in Musculoskeletal open surgery as the series cited above are very small and there is no comparative RCT between local adjuvant therapies including CA. One-hundred-and-eighty-three patients were treated with Cryoablation from 2000 and 2018 in the Musculoskeletal Tumours Surgery Unit of Careggi (Florence) and the University 2nd Clinic of Pisa. In our study group, 38 patients (26.6%) were affected by bone metastasis, 16 patients (11.1%) by aneurismal bone cysts or angiomas, 22 patients (15.4%) by low-grade malignant musculoskeletal tumours, 2 patients (1,4%) by fibromatosis, 63 patients (44.1%) by benign musculoskeletal tumours (principally Giant Cell Tumours-GCT) and 2 patients (1.4%) by Osteosarcomas. In 125 cases (87.4%), CA has been used as an adjuvant therapy, in 12 cases (8.4%) as a percutaneous ablation therapy and in 6 cases (4.2%) as adjuvant to remove tumoral lesions 'en bloc' or as a 'poor technique' for its sterilizing effect on previously resected bones. Mean follow-up was 10 years. Twenty-three patients (16%) were classified as Alive with Disease (AWD) due to local recurrence or tumour progression (14 metastases, 5 low-grade malignant bone tumours, 4 Giant Cell Tumours). Eight patients died due to the disease (6 metastases, 2 osteosarcomas), while 1 died from leukaemia. One-hundred-and-eleven patients (78%) were classified as Continues Disease Free (CDF). All patients reported decrease in pain-related symptoms after surgery and all surgeons reported better control of blood loss. Three cases (2%) of local skin necrosis or wound dehiscence were reported. No local recurrences were reported after fibromatosis ablation. Our results confirm that CA could be considered as a safe and effective technique to treat various conditions as adjuvant and palliative therapy. In particular, in open surgery, cryotherapy as an adjuvant treatment could lead to very low rates of recurrence in locally aggressive tumours like Giant Cell Tumours. These results could be generalized but a better understanding about indications and outcomes can be reached studying CA in specific populations with comparation to other adjuvant techniques.

Combining of serial embolization and denosumab for large sacropelvic giant cell tumor: Case report of 3 cases.

RATIONALE: Both serial arterial embolization (SAE) and denosumab have been proved to be effective in treatment for giant cell tumor (GCT). There is potential synergic effect of combining two methods. The purpose of current study is to justify a new treatment strategy of combination of SAE and denosumab as neoadjuvant or stand-alone treatment for large sacropelvic giant cell tumor. PATIENT CONCERNS: Pelvic and sacral GCTs tend to be very large size and vascular. The concerns of surgical treatment were invasiveness of extensive surgery, intraoperative hemorrhage, nerve function jeopardized and local recurrence. However, SAE alone may not be adequate for complete removal of the tumor. DIAGNOSES: All the three cases were proved to be GCT by core-needle biopsy. Post-treatment pathological change was confirmed by further biopsy. INTERVENTIONS: The patient in Case 1 diagnosed of large recurrent sacral GCT received 6 times of endovascular embolizations with 2-month interval and started on denosumab simultaneously after first session of embolization. The second case was a 22-year-old female presented with a massive iliosacral tumor. SAE was performed for 3 sessions and the denosumab was started simultaneously. The patients was on treatment for half year. Both patients experienced a dramatic decrease in symptoms and concomitant improvement in function after the first embolization and weekly injection of denosumab. Tumor removal was performed on patient in case 2. The last case was a pelvic GCT and the patient received SAE and denosumab for half year. The tumor was then removed with purpose of complete cure. OUTCOMES: The first patient was still on denosumab with stable tumor. The other two patients were both free of recurrence after surgical removal of the tumors. No denosumab was used postoperatively. LESSONS: We reported the first three cases treated by combination of SAE and denosumab in the literature and aim to raise an alternative method for large GCT at challenging anatomical locations, for which surgery would carry significant risk. SAE and denosumab can synergically promote sclerosis and result in significant decrease in pain. It is reasonable to consider using SAE combined with denosumab neoadjuvantly to reduce the extensiveness and morbidity of surgery, however further investigation is warranted.

Tumor de células gigantes vertebral: una causa rara de cervicalgia / Giant cell tumor of the spine: a rare cause of cervical pain

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Treatment of a skull-base giant cell tumor with endoscopic endonasal resection and denosumab: case report.

A 34-year-old man with a 1-week history of diplopia was referred to the authors' hospital. Neurological examination revealed left abducens nerve palsy. Computed tomography showed a lesion in the left sphenoid sinus involving the medial wall of the left internal carotid artery (ICA) and osteolytic change at the clivus bordering the lesion. Magnetic resonance imaging demonstrated an extensive soft-tissue mass occupying the left sphenoid sinus. Surgical intervention by the endoscopic transnasal method allowed most of the lesion to be removed. Only the portion attached to the medial wall of the ICA was not removed. Postoperatively, the lesion was diagnosed as a giant cell tumor (GCT) and the patient received 120 mg of subcutaneous denosumab every 4 weeks, with additional doses on Days 8 and 15 during the first month of therapy. MRI a week after starting denosumab revealed shrinkage of the initially fast-growing residual tumor. The patient was discharged upon completion of the third denosumab administration. GCT is an aggressive stromal tumor developing mainly in young adults. Complete resection is recommended for GCT in the literature. However, size and location of the CGT often limit this approach. Various adjuvant treatments for skull base GCTs have been reported, including radiation and chemotherapy. However, the roles of adjuvant therapies have yet to be clearly defined. Denosumab, a monoclonal antibody, was recently approved for GCT in several countries. Denosumab may permit less invasive treatments for patients with GCTs while avoiding deleterious outcomes, and may also limit disease progression and recurrence.

Isolated limb perfusion as a treatment option for rare types of tumours.

BACKGROUND: Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours. METHODS: Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively. RESULTS: The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B-cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%). CONCLUSIONS: These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed.

Treatment options and prognosis for repeatedly recurrent giant cell tumor of the spine.

BACKGROUND: Giant cell tumor of the spine has high rate of postoperative recurrence. There are not much published studies on repeatedly recurrent GCTS (RRGCTS). Also, there are controversies as to the prognostic factors and treatment options for RRGCTS. METHODS AND MATERIALS: A retrospective survival analysis between 2000 and September 2014 was performed on the 74 times of in-hospital treatment of the 21 patients. Recurrence-free survival was defined as the time between the date of surgery and the date of recurrence. Factors with P values <0.05 in univariate analysis were subjected to multivariate analysis by means of proportional hazard analysis. RESULT: A total of 21 patients comprising ten males and 11 females with a mean age of 29.7 years (range 15-49) were included, with a total of 74 times of surgery performed. Eighteen patients had no evidence of disease. Univariate and multivariate analysis suggested that total spondylectomy and bisphosphonate therapy were independent prognostic factors for better RFS in RRGCTS patients. CONCLUSION: Patients of RRGCTS are suitable for further surgical treatment with relatively good healing process and restoration of nervous function. Early diagnosis of recurrence may be associated with better prognosis. Total spondylectomy in combination with bisphosphonate therapy could reduce postoperative recurrence rate.

Giant-cell tumor: analysis on the importance of early diagnosis and the epidemiological profile / Tumor de células gigantes: análise sobre importância do diagnóstico precoce e perfil epidemiológico

This study aimed to ascertain the relationship between early diagnosis of giant-cell tumors (GCT) and their prognosis, by correlating the time of symptom onset with the staging of the injury (through the Campanacci classification at the time of diagnosis), and with the type of treatment. The secondary objective of the study was to outline the epidemiological profile of patients with GCT in the region where the data were gathered, and to compare them with data in the literature. METHODS: The authors present an evaluation on 61 patients diagnosed with bone GCT, with regard to the site of involvement, age, initial symptoms, time of symptom onset, classification and type of treatment, among patients attended between May 1994 and August 2009. RESULTS: The threshold indicated as the limit for Campanacci stage I tumors to be the commonest diagnosis, with a 98.2% chance that the treatment would be non-aggressive, was 2 months after symptom onset. This finding was statistically significant (p = 0.017). Every additional month increased the chance that a patient would be diagnosed with an advanced-stage tumor by 10.94%, in relation to the chances of having the other two stages of the tumor. CONCLUSION: The study result not only suggests that the alternative hypothesis that the earlier the diagnosis of GCT is, the less severe the lesion will be, has been confirmed; but also especially predicts the relationship between the time of symptom appearance and the severity of the tumor.

Presumir a relação entre o diagnóstico precoce do tumor de células gigantes (TCG) e o seu prognóstico, relacionar o tempo de surgimento dos sintomas com o estadiamento da lesão, por meio da classificação de Campanacci no momento do diagnóstico, e com tipo de tratamento. O objetivo secundário do estudo é traçar o perfil epidemiológico dos pacientes com TCG da região onde foram colhidos os dados e compará-lo com dados da literatura. MÉTODOS: Avaliação de 61 pacientes diagnosticados com tumor de células gigantes ósseo quanto ao local de acometimento, idade, sintomatologia inicial, tempo do surgimento dos sintomas, classificação e tipo de tratamento em pacientes atendidos entre maio de 1994 e agosto de 2009. RESULTADO: Aponta o marco de dois meses após o início da sintomatologia como data limite, quando seria mais comum o diagnóstico de tumor estágio I de Campanacci e com 98,2% de chance de ser tratado de modo não agressivo, dados com relevância estatística (p = 0,017). A cada aumento de um mês a chance de um paciente ser diagnosticado com tumor em estágio avançado é 10,94% maior do que em relação aos outros dois estágios do tumor. CONCLUSÃO: O resultado do estudo sugere não somente a confirmação da hipótese opcional de que quanto mais precoce o diagnóstico de TCG, menos grave é a lesão, mas, principalmente, prediz a relação do tempo de surgimento do sintoma com a gravidade do tumor.

Giant Cell Tumors of the Bone With Pulmonary Metastasis.

Giant cell tumors of the bone are benign but locally aggressive, and they rarely metastasize to the lungs. The purpose of this study was to retrospectively review the clinical presentation, long-term outcomes, and treatment of pulmonary metastasis of these tumors. Between 1991 and 2004, a total of 168 patients with giant cell tumors of the bone were treated at the authors' institution, 7 of whom developed lung metastasis. Four of the 7 patients were men, and mean age of these patients at initial surgery was 40 years (range, 19-56 years). All patients underwent wide excision and reconstruction or curettage and bone grafting for the bony lesions. Lung metastases were detected at a mean of 44 months after the treatment of bone lesions. Five patients had multiple metastases, and 2 had solitary pulmonary metastases. Six of these patients underwent delayed treatment, locally aggressive, or multiple recurrent and surgical procedures. All of the aforementioned procedures had similar risk factors to those previously reported in the literature. One patient had multiple giant cell tumors of the bone. At last follow-up, 2 patients had died due to complications from the pulmonary metastases or chemotherapy. One patient underwent a metastasectomy 4 years after treatment due to the progression of pulmonary metastasis. The remaining 4 patients were alive and healthy after chemotherapy or conservative treatment. Therefore, early detection, adequate treatment of the primary bone lesion, conservative treatment of lung metastases, and regular long-term follow-up are recommended.

Squamous cell carcinoma of lung associated with osteoclast-like giant cells: report of a case.

Resently, we treated a 69-year-old patient with squamous cell carcinoma of lung with osteoclast-like giant cells which were similar with the giant cell tumor of bone. The clinical and pathological characteristics of this case were presented, and the literatures were reviewed. The tumor differed histologically from the pleomorphic carcinoma, which occurs most commonly in the lung and showed diverse pleomorphic manifestation with benign looking osteoclast-like multinucleated cells and bizarre giant cells. In addition, undifferentiated carcinoma with a sarcoma-like appearance containing small areas of papillary adenocarcinoma was evident in the tumor. Histological features and immunohistochemical staining could be helpful in differential diagnosis.

Giant cell variant of malignant fibrous histiocytoma of male breast: A rare case report.

Malignant fibrous histiocytoma (MFH) is the most common form of soft tissue sarcoma during middle and late adulthood in the deep connective tissue of the extremities, abdominal cavity, and retroperitoneum. However, primary breast sarcoma is a rare disease entity, comprising less than 1% of all breast malignancies. MFH of the male breast is very rare. We present a case of MFH of giant cell variant of the right breast in a 50-year-old male who presented with a painless lump. Following cytological investigation, simple mastectomy was performed. Immunohistochemical staining confirmed the diagnosis.

Giant Cell Tumor of the Larynx Treated by Surgery and Adjuvant Denosumab: Case Report and Review of the Literature.

Giant cell tumor of the larynx (GCTL) is a rare entity; only 34 cases have been reported in the literature. We report a case of GCTL in a 46 year-old male presenting clinical, radiographic, histological and therapeutic features. Previously reported cases are also reviewed.